Cytomegalovirus infection in IBD patients undergoing anti-TNF-alpha therapy

CMV infection is frequent in pts treated with immunosuppressive drugs and may be associated with steroid refractoriness and poor outcome in IBD pts. No data are available on the effect of anti-TNF- treatment on prevalence and clinical course of CMV infection and disease in IBD. We assessed the severity of active CMV infection and disease in 11consecutive pts with ileocolonic/colonic Crohn’s disease and 4 pts with ulcerative colitis (10 males, 5 females, mean age 50,2 18.1 SD) before and after a standard 3-infusion course of Infliximab for fistulizing disease in 8 pts, steroid-dependent/refractory disease in 7. Six pts were on cortisone during the first observation and 9 on azathioprine. All pts received azathioprine after the first anti-TNF infusion. Seroprevalence of CMV infection was evaluated by serology. Active CMV infection was diagnosed by means of pp65-antigenemia (pp65-AG). CMV disease was assessed on haematoxylin/ eosin-stained colonic biopsies, quantisation of CMV DNA by a quantitative PCR kit (Amplification set CMV Hybridoquant, Bioline, Italy), allowing amplification of a minimum of 100 copies/ug of DNA isolated from colonic biopsies. Results: All pts but 2 were positive for anti-CMV. One patient had positive pp65-AG before and after Infliximab. In 2 pts CMV was diagnosed by conventional histology. CMV DNA was present before therapy in 3 pts (130-1340 copies/ug of DNA) and in 2 of them only (410 and 1300 copies/ug DNA) after therapy. The histological inflammation in colonic tissue improved after anti-TNF- in all CMV-positive pts but one of the 2 pts positive for CMV DNA in which it remained unchanged. Discussion: The prevalence of active CMV infection and disease assessed by means of pp65- AG, conventional histology and competitive quantitative PCR on colonic DNA extracts didn’t vary after Infliximab. In pts who had active CMV infection and disease before anti-TNF- , the severity of colonic mucosal inflammation did not worsen and the number of copies/ng DNA from colonic DNA extracts did not increase following therapy. This proved true also in the 2 pts with severe colitis and serum or tissue CMV DNA positivity. Conversely one pt became CMV DNA-negative after the course of anti-TNF . Despite the reports of increased active CMV infection resulting from post-transplant immunosuppression, these preliminary data suggest that the problem may not be relevant in IBD patients undergoing a course of cortisone, azathioprine and anti-TNF- .